Plasma Concentration Determination of Carboplatin by 2 Administration Routes in Female Rats in vivo and Study on the Pharmacokinetics / 中国药房

ABSTRACT

OBJECTIVE:To establish a method for the plasma concentration determination of carboplatin,and study the phar-macokinetics of carboplatin in female rats after intravenous injection and intraperitoneal injection. METHODS:HPLC was per-formed on the column of Agilent TC-C18 with mobile phase of methanol-water(595,V/V)at a flow rate of 1.0 mL/min,detection wavelength was 229 nm,and column temperature was 25 ℃. The inner standard was 5-bromouracil,and injection volume was 20 μL. 24 SD rats were randomly divided into 4 groups,6 in each group. The rats were intravenously injected and intraperitoneally in-jected carboplatin 20,40 mg/kg respectively. 0.5 mL blood sample was taken from eyes before administration and after administra-tion of 0.25,0.5,1,1.5,2,4,6,8,10,12 h. The plasma concentration of carboplatin was determined,and DAS 2.0 was used to calculate the pharmacokinetic parameters. RESULTS:The linear range of carboplatin in plasma was 0.30-60.00 μg/mL (r=0.9991);RSDs of intra-day,inter-day precision were lower than 10%(n=5);RSD of peak area in stability test was lower than 10%(n=5);method recovery was 98.7%-102.4%(RSD≤6.08%,n=5),and extraction recovery was 83.38%-85.45%(RSD≤5.97%,n=5). AUC0-12 h of carboplatin 20,40 mg/kg by intravenous injection and intraperitoneal injection in female rats were (15.503 ± 4.172),(23.402 ± 4.266),(6.716 ± 2.306),(9.384 ± 2.205)μg·h/mL;AUC0-∞ were (16.424 ± 4.846),(23.404 ± 4.266),(6.790±2.378),(9.765±2.095)μg·h/mL;t1/2z were(1.246±0.765),(0.394±0.058),(0.513±0.156),(0.884±0.460) h;and tmax were(0.700±0.274),(0.400±0.335),(0.542±0.368),(0.833±0.289)h,respectively. CONCLUSIONS:The meth-od is simple,economic and accurate,with suitable internal standard,and can be used for the plasma concentration determination of carboplatin in female rats and the pharmacokinetic studies.